An ongoing study on the regulation of beta1 and beta2-adrenergic receptors (beta1AR and beta2AR) and receptor gene expression by interleukin-1alpha (IL-1a) in A549 has been completed and the results published. Briefly, A549 cells in preconfluent cultures had fewer beta1AR than beta2AR, but lost most of their beta2AR upon reaching confluency. Incubation of preconfluent cells for 24 hr with 20 pM of human recombinant IL-1a did not modify the density of either of the betaAR subtypes. In contrast, in confluent cells IL-1a significantly increased the density of beta2AR, while the density of beta1AR and the antagonist affinities of both receptors remained unaltered. The IL-1a-induced increase in beta2AR density in confluent cells was antagonized in a induced increase in a concentration dependent manner by a recombinant protein antagonist of type I IL-1 receptors (IC50: 0.2 nM). The IL-1a-induced increase in beta2AR density was preceded by an increase in the steady state level of beta2AR mRNA, while levels of beta1AR mRNA remained unchanged. The increase in beta2AR mRNA level by IL-1a was due to an increase in both the rate of transcription and the stability of the beta2AR mRNA. These observations indicate that activation of type I IL-1 receptors in A549 cells leads to a cell density-dependent, selective upregulation of beta2AR, and that the mechanism of this effect involves increased transcription of the beta2AR gene, as well as an increase in its stability.